|
|
 |
Protein dynamics key to designing more efficient enzymes
Life at the molecular level is made possible by thousands to millions of individual protein complexes that work together as highly efficient machines. A sub-group of these molecules called enzymes are particularly intriguing, as they catalyze the wide variety of biochemical reactions that occur inside a cell. Enzymes are remarkable catalysts, they can accelerate biochemical reaction by more than a trillion fold. For more than a century, enzymes have been viewed as static entities and their high catalytic power has been explained on the basis of direct structural interactions between the enzyme and the substrate. Theoretical methods and computational simulations performed at Oak Ridge National Laboratory (ORNL) are now providing fascinating and novel details into the working of enzymes, which is changing the way scientists understand these molecules.
Performed on the National Center for Computational Sciences’ (NCCS) Jaguar supercomputer, these simulations are revealing that proteins are dynamically active entities that are constantly undergoing internal fluctuations, similar to leaves on a tree fluttering in the wind. These investigations are leading to an integrated view of protein structure, dynamics and function, where proteins such as enzymes are considered as dynamically active assemblies and internal vibrations are closely linked to function such as enzyme catalysis. Protein vibrations are internal motions that occur million times or more every second. ORNL’s investigations have revealed that a select number of these vibrations are closely tied to the efficiency of the enzyme function and therefore are an integral part of the protein structure. These vibrations are responsible for transferring energy from the solvent to the active-site, where this energy is used to overcome the activation energy barrier, therefore, promoting the reaction. It may soon be possible to manipulate the proteins by vibrationally exciting them to increase the rate of enzyme reactions.
This break-through in understanding of enzymes has important implications for health and medicine, energy, and the environment. Once the detailed nature of the protein vibrations is understood, this knowledge will be vital in designing new enzymes for industrial processes as well improving the efficiency of existing ones. For example, engineered cellulases may provide the technological solution for lowering the cost of production of ethanol from cellulose found in the abundantly available biomass.
For more information, please contact:
Pratul Agarwal
|
|
